Cardiovascular Research:3D scans spot earliest signs of heart disease ♦ Lower systolic blood pressure reduces risk of hypertension complication ♦ Low physical activity responsible for 17 percent of cardiovascular deaths

Low physical activity responsible for 17 percent of cardiovascular deaths in Argentina Low levels of physical activity are responsible for 17 percent of cardiovascular deaths in Argentina.

Lower systolic blood pressure reduces risk of hypertension complication Lowering systolic blood pressure below the currently recommended target can reduce the risk of left ventricular hypertrophy (LVH), the most common complication of high blood pressure.

Favorable one-year clinical outcomes for catheter-based aortic valve replacement with latest generation of device Findings from the PARTNER II Trial, which examined one-year clinical outcomes among high-risk or inoperable patients who received TAVR with the latest generation of balloon-expandable (SAPIEN 3) device, are being released by researchers, suggesting that the new device offers promising outcomes for patients.

Zebrafish study sheds new light on human heart defects Researchers working with zebrafish have published a study providing new insights into the causes of the congenital heart defects associated with a rare developmental disorder. The disorder, Cornelia de Lange Syndrome (CdLS), is estimated to occur in up to one in 10,000 births worldwide. CdLS causes a range of developmental anomalies, both physical and cognitive, and up to 70 percent of people with CdLS have congenital heart defects.

3D scans spot earliest signs of heart disease People with high blood pressure develop changes in their hearts even before symptoms appear, new research shows. These changes are known to put people at risk of dying early, and the new work suggests it is possible for doctors to recognize such signs of heart disease earlier than they can today -- by examining detailed images of the heart.

Health News: MRSA in pork:♦ Patients give high marks to prepping for surgery online ♦ Patients give high marks to prepping for surgery online

MRSA in pork: farming leaders join calls for clampdown on illegal antibiotic use

Britain’s farming leaders are urging the government to clamp down on the illegal use of powerful antibiotics following a Guardian investigation that found evidence that the superbug MRSA – linked to the overuse of antibiotics in livestock – has entered the UK’s food chain.

Thick cortex could be key in Down syndrome The thickness of the brain's cerebral cortex could be a key to unlocking answers about intellectual development in youth with Down syndrome. It could also provide new insights to why individuals with this genetic neurodevelopmental disorder are highly susceptible to early onset Alzheimer's disease.

Zebrafish provide a novel model to study short bowel syndrome Investigators are providing new hope for babies with short bowel syndrome (SBS) by developing a novel model of SBS in zebrafish,

'Real world' link between type 2 diabetes, low blood sugar risk Hypoglycaemia is an issue amongst people with type 2 diabetes, particularly for those on insulin, yet is still fairly common for other treatment regimens. Now the hypoglycaemic events in the ‘real world’ type 2 diabetes population have been examined in a first-of-its-kind review. The study highlights the need for patient education to raise awareness of hypoglycaemia and for healthcare professionals to consider a patient’s hypoglycaemia risk when prescribing diabetes treatments.

Patients give high marks to prepping for surgery online First-time surgery can be concerning to any patient. Knee surgery -- even arthroscopic surgery to treat a torn meniscus -- can require significant preparation and rehabilitation. According to a new study, a web-based tutorial can not only increase a patient's understanding of the surgery but also provide a better experience.

How Genes Affect Facial Development

Experiments in zebrafish shed light on how the structure of the face forms. Problems with equivalent genes in people can cause facial defects and other developmental issues.

DiGeorge syndrome (also called 22q11.2 deletion syndrome, among other names) affects an estimated 1 in 4,000 people. Children with DiGeorge syndrome often have facial defects that include an undeveloped chin, heavy eyelids, and ears that are rotated back. Other common signs and symptoms include heart defects and recurrent infections caused by problems with the immune system.

Zebrafish studies can yield insight into human development.

Structures within the head and neck develop from embryonic features called pharyngeal pouches. These emerge from the endoderm, the inner layer of the embryo. DiGeorge defects are thought to be at least partly due to malformation of these pouches. However, the details of these developmental steps remain poorly understood.

To understand how genes cause complex developmental problems, researchers often use model systems, such as fish, worms, and mice. DiGeorge syndrome has been associated with deletion of a region of chromosome 22, which contains the TBX1 gene. Zebrafish with Tbx1 mutations have severe defects in pouch formation and facial skeletal development. Similarly, Tbx1 mutant mice lack pouches and have defects that mimic those of people with DiGeorge syndrome.

Drs. Chong Pyo Choe and J. Gage Crump at the University of Southern California used zebrafish to investigate how Tbx1 might control craniofacial formation. Their study was supported in part by NIH’s National Institute of Dental and Craniofacial Research (NIDCR). Results were published in the September 2014 issue of Development.

In previous work, the team found that the genes fgf8a and wnt11r are expressed in the mesoderm, the middle layer of the embryo, when pouches begin to form. Both genes are required for pouch development. In this study, the researchers showed that Tbx1 is required for the expression of both genes in the developing mesoderm. Restoring fgf8a and wnt11r expression in the mesoderm bypasses mutant tbx and rescues its effects on pouch development.

Using advanced time-lapse imaging techniques to track individual cells, the scientists showed that pouch-forming epithelial cells from the endoderm migrate toward areas expressing fgf8a in adjacent mesoderm. Wnt11r enables these cells to respond to Fgf8a and begin the process of forming pouches.

This research showed that Tbx1, acting through fgf8a and wnt11r, functions in the facial mesoderm to coordinate multiple steps in pouch formation. “Whereas it has been recognized that mutations in TBX1 underlie DiGeorge syndrome in patients, our study reveals how this master control gene works to organize the complex cellular rearrangements that build the face,” Crump says.

Defects in pouch development underlie several human birth defects. Continuing studies in model systems such as zebrafish will help us understand the signaling pathways involved and yield critical insights into the origins of many congenital disorders.

Zebrafish Help Finding Possible Cures for Childhood Epilepsy

Study finds zebrafish model may help identify treatments for a severe form of childhood epilepsy. Results of a study in “Nature Communications” suggest that zebrafish carrying a specific mutation may help researchers discover treatments for Dravet syndrome (DS), a severe form of pediatric epilepsy that results in drug-resistant seizures and developmental delays.

Scott C. Baraban, Ph.D., and his colleagues at the University of California, San Francisco (UCSF), carefully assessed whether the mutated zebrafish could serve as a model for DS, and then developed a new screening method to quickly identify potential treatments for DS using these fish. laboratory in 2005.

The researchers found that the zebrafish that were engineered to have a gene mutation that causes DS in humans exhibited some of the same characteristics, such as spontaneous seizures, commonly seen in children with DS. Unprovoked seizure activity in the mutant fish resulted in hyperactivity and whole-body convulsions associated with very fast swimming. These types of behaviors are not seen in normal healthy zebrafish.

“We were also surprised at how similar the mutant zebrafish drug profile was to that of Dravet patients,” said Dr. Baraban. “Antiepileptic drugs shown to have some benefits in patients also exhibited some antiepileptic activity in these mutants. Conversely, many of the antiepileptic drugs that do not reduce seizures in these patients showed no effect in the mutant zebrafish.”

In this study, the researchers developed a fast and automated drug screen to quickly test the effectiveness of various compounds in mutant zebrafish. The researchers tracked behavior and measured brain activity in the mutant zebrafish to determine if the compounds had an impact on seizures.

“The mutants seize often, so it is relatively easy to monitor their seizure behavior at baseline and then again after a drug application,” said Dr. Baraban. “Using zebrafish  we can accurately quantify this seizure behavior. In this way, we can test almost 100 fish at one time and quickly determine whether a drug candidate has any effect on these spontaneous seizures.”

In the first such application of this approach, UCSF researchers screened 320 compounds and found that clemizole was most effective in inhibiting seizure activity. Clemizole is approved by the U.S. Food and Drug Administration and has a safe toxicology profile. “This finding was completely unexpected. Based on what is currently known about clemizole, we did not predict that it would have antiepileptic effects,” said Dr. Baraban.

These findings suggest that mutant zebrafish may serve as a good model of DS and that the drug screen may be effective in quickly identifying novel therapies for epilepsy.

Dr. Baraban also noted that someday these experiments can be “personalized,” by looking at mutated zebrafish that use genetic information from individual patients.

Dr. Fureman noted that these findings not only describe a novel model of Dravet syndrome, but the positive results with an unexpected FDA-approved drug may lead to new therapeutic avenues. “There is more work to be done, but I am very pleased to see these initial results.For more information about Dravet syndrome and epilepsy, please visit:

http://www.ninds.nih.gov/disorders/dravet_syndrome/dravet_syndrome.htm

• http://www.ninds.nih.gov/disorders/epilepsy/epilepsy.htm